Background:  HIV disease has been associated with accelerated loss of renal function. Several factors have been implicated in this process, including HIV-associated immunodeficiency, viral replication, direct toxicity of ART, and higher rates of non-AIDS related co-morbidities. To more carefully elucidate the roles of these factors in renal disease, we compared the rates of kidney function decline in four well-characterized groups of HIV-infected patients, each defined by the degree of viral replication in the presence or absence of ART.

Methods:  We estimated rates of change in kidney function among 615 patients enrolled in the SCOPE cohort using a repeated measures linear mixed effects model. Kidney function was estimated using the Modification of Diet in Renal Disease Equation, which calculates the glomerular filtration rate (GFR) based on age, gender, race, and standardized serum creatinine. We stratified our analysis into the following groups based on treatment status and plasma HIV RNA level (≤ vs >1000 copies/mL):  untreated controllers, untreated noncontrollers, ART-controllers, and ART-noncontrollers. In multivariable longitudinal models, we adjusted for age, sex, race, and time-updated CD4 count, viral load, ART, and co-morbid conditions.

Results:  After multivariate adjustment, the rate of GFR decline was lowest among untreated controllers, highest in untreated noncontrollers, and intermediate in the 2 treated groups. Rates of GFR decline in the untreated noncontrollers, the ART-controllers, and the ART-noncontrollers were –5.8 (95%CI –8.1 to –3.4), –5.2 (95%CI –7.5 to –3.0), and –5.5 (95%CI –7.6 to –3.3) mL/min/1.73m²/year relative to untreated controllers, respectively. Despite suppressed viremia, ART controllers experienced continued GFR loss (–1.6, 95%CI –2.5 to –0.7 mL/min/1.73m²/year). In these patients, transient increases in viral load rather than CD4⁺ count was associated with GFR decline.

Conclusions:  Although ART appears to help curb kidney function decline among those with uncontrolled viremia, patients who have achieved durable viral suppression continue to lose kidney function above age-expected norms. Overall kidney function loss is more closely associated with viremia, whereas the level of immunodeficiency (as defined by CD4⁺ count) does not appear to be a major prognostic factor in either untreated or treated disease.